Inflammatory Bowel Disease E Rahimi, MD Assiatant Professor Department Of Internal Medicine MUK

Inflammatory Inflammatory Bowel DiseaseBowel Disease

E Rahimi, MDE Rahimi, MDAssiatant ProfessorAssiatant Professor

Department Of Internal MedicineDepartment Of Internal Medicine

MUKMUK

Inflammatory Bowel Disease Inflammatory Bowel Disease (IBD)(IBD)

Ulcerative colitis Ulcerative colitis and and Crohn's Crohn's diseasedisease

Introduction Introduction

IBD characterized by a tendency for IBD characterized by a tendency for chronicchronic or or relapsing relapsing immune immune activation and inflammation within activation and inflammation within the GIT.the GIT.

CrohnCrohn’’s disease s disease (CD)(CD) and ulcerative and ulcerative colitis colitis (UC) (UC) are the 2 major forms of are the 2 major forms of idiopathic IBD.idiopathic IBD.

Less common entities are:Less common entities are:

IntroductionIntroduction

EyeEyeinflammationinflammation**

Liver andLiver andbile ductbile duct

inflammationinflammation

Skin lesionsSkin lesions

Arthritis and Arthritis and joint painsjoint pains

KidneyKidneystonesstones

Growth failureGrowth failurein childrenin children

LowerLowerbone densitybone density**

SubfertilitySubfertility**

IBD: Systemic IBD: Systemic ComplicationsComplications

**Higher incidence in womenHigher incidence in women..

GallstonesGallstones

OvariesOvaries

UterusUterus

Epidemiology Epidemiology

Epidemiology Epidemiology

Genetics

EtiologyEtiology

Pathogenesis

The mucosa of CD patients is dominated by Th1

(T helper), which produce interferon-γ and IL-2.

In contrast, UC dominated by Th2 phenotype, which produce transforming growth factor (TGF-) and IL-5.

Activation of Th1 cells produce the down-regulatory cytokines IL-10 and TGF-.

Pathogenesis

A sequential casιade of inflammatory A sequential casιade of inflammatory mediators extends the response; each step is mediators extends the response; each step is a potential target for therapy. a potential target for therapy.

Inflammatory cytokines such as IL- l Inflammatory cytokines such as IL- l ，， IL-IL-66 ，， and TNF have divers, effects on tissues.and TNF have divers, effects on tissues.

They promote They promote fibrogenesis,fibrogenesis, collagen collagen production production activation of tissue activation of tissue metalloproteinasesmetalloproteinases ，， and the production of and the production of other inflammatory mediators; they also other inflammatory mediators; they also activate the activate the coagulation cascadecoagulation cascade..

Pathogenesis

These cytokines are normally produced in These cytokines are normally produced in response to infection but are usually response to infection but are usually turned turned off off or inhibited at the appropriate time to or inhibited at the appropriate time to limit tissue damage.limit tissue damage.

In IBD their activity is not regulated, In IBD their activity is not regulated, resulting in an imbalance between the resulting in an imbalance between the proinflammatory and antiinflammatory proinflammatory and antiinflammatory medíators.medíators.

Therapíes such as the 5 – aminosalicylic acid Therapíes such as the 5 – aminosalicylic acid (5 -ASA) compounds and glucocorticoids are (5 -ASA) compounds and glucocorticoids are potent inhibitorspotent inhibitors

Environmental Environmental PrecipitantsPrecipitants

Factors: NSAIDs use (?altered intestinal

barrier), and Early appendectomy (increase UC

incidence) Smoking (protects against UC but

increases the risk of CD).

CD: PATHOLOGY

Early Findings: Aphthous ulcer. The presence of granulomas

Late findings: Linear ulcers. The classic cobble stoned appearance

may arise. Transmural inflammation Sinus tracts, and strictures. Fibrosis.

UC: PATHOLOGY The inflammation is predominantly

confined to the mucosa. Non-specific (can be seen with any

acute inflammation) The lamina propria becomes edematous. Inflammatory infiltrate of neutrophils Neutrophils invade crypts, causing

cryptitis & ultimately crypt abscesses. Specific (suggest chronicity):

Distorted crypt architecture, crypt atrophy and a chronic inflammatory infiltrate.

UCUC

Diagnosis Diagnosis

Exclude other possibilities (need Exclude other possibilities (need good history, physical exam, labs, good history, physical exam, labs, imaging and endoscopy with biopsy)imaging and endoscopy with biopsy)

There are many distinguishing There are many distinguishing features of CD and UC.features of CD and UC.

In about 5% it is classified as In about 5% it is classified as indeterminate because of indeterminate because of overlapping features.overlapping features.

Distinguishing characteristics of Distinguishing characteristics of CD and UCCD and UC

Feature CDUC

Location SB or colonOnly colon (rarely

“backwash ileitis”

Anatomic distribution

Skip lesionsContinuous, begins distally

Rectal involvement

Rectal spareInvolved in >90%

Gross bleeding

Only 25%Universal

Peri-anal disease

75%Rare

Fistulization Yes No

Granulomas 50-75%No

Endoscopic features of CD Endoscopic features of CD and UCand UC

Feature CDUC

Mucosal involvement

Discontinuous

Continuous

Aphthous ulcers

Common Rare

Surrounding mucosa

Relatively normal

Abnormal

Longitudinal ulcer

Common Rare

Cobble stoningIn severe cases

No

Mucosal friability

Uncommon Common

Vascular pattern

Normal distorted

Pathologic features of CD Pathologic features of CD and UCand UC

Feature CDUC

Transmural inflammation

Yes Uncommon

Granulomas 50-75%No

Fissures Common Rare

Fibrosis Common No

Submucosal inflammation

Common Uncommon

Radiologic features of CD Radiologic features of CD and UCand UC

Feature CDUC

Nodularitygranularity

cobble stoningstring sign of SB

Collar button ulcers

UCUC

CDCD

UC: PresentationUC: Presentation Must exclude infectious cause before Must exclude infectious cause before

making Dx.making Dx. Rectal Bleeding Rectal Bleeding Diarrhea:Diarrhea:

frequent passage of loose or liquid stool, often frequent passage of loose or liquid stool, often associated with passing large quantities of associated with passing large quantities of mucus.mucus.

Abdominal Pain:Abdominal Pain: it is not a prominent symptom. it is not a prominent symptom.

Anorexia, nausea, feverAnorexia, nausea, fever……

DDX of UCDDX of UC

InfectiousInfectious Drug inducedDrug induced Microscopic colitisMicroscopic colitis

UC: PresentationUC: Presentation

UC: PresentationUC: Presentation

About 40-50% of patients have About 40-50% of patients have disease limited to the rectum and disease limited to the rectum and rectosigmoidrectosigmoid

30-40% have disease extending 30-40% have disease extending beyond the sigmoid but not involving beyond the sigmoid but not involving the whole colonthe whole colon

20% have a total colitis.20% have a total colitis.

CDCD

Anatomic Anatomic distributiondistribution

CD activity CD activity indexindex

DDx DDx (lymphoma, (lymphoma, Yersinea Yersinea Enterocolitis, Enterocolitis, TB)TB)

CD: clinical CD: clinical presentationspresentations

Disease of the ileum: May present initially with a small bowel

obstruction. Patients with an active disease often present

with anorexia, loose stools, and weight loss. Perianal disease

In 24% of patients with CD. Skin lesions include superficial ulcers, and

abscesses. Anal canal lesions include fissures, ulcers, and

stenosis.

CD ilitis: DDxCD ilitis: DDx

LymphomaLymphoma

Yersinea Enterocolitis andYersinea Enterocolitis and TBTB

CD: clinical CD: clinical presentationspresentations

colonic disease The typical presenting symptom is diarrhea,

occasionally with passage of obvious blood. proctitis

May be the initial presentation in some cases of CD

Extra-intestinal manifestations Extra-intestinal manifestations of IBDof IBD

Arthritis:Arthritis: Peripheral arthritis, usu paralels the disease Peripheral arthritis, usu paralels the disease

activityactivity Ankylosing Spondylitis, 1-6%, sacroiliitisAnkylosing Spondylitis, 1-6%, sacroiliitis

Ocular lesions:Ocular lesions: Iritis (uvietis) (0.5-3%), episcleritis, keratitis,Iritis (uvietis) (0.5-3%), episcleritis, keratitis,

Skin and oral cavity:Skin and oral cavity: Erythema nodosum 1-3%Erythema nodosum 1-3% Pyoderma Gangrenosum 0.6%Pyoderma Gangrenosum 0.6% Aphthus stomatitis, metastatic CD.Aphthus stomatitis, metastatic CD.

DermatologicDermatologic Erythema nodosum (EN) Erythema nodosum (EN) occurs in up to occurs in up to

15% of CD patients and 10% of UC patients. 15% of CD patients and 10% of UC patients. Attacks usually correlate with bowel activity; Attacks usually correlate with bowel activity;

skin lesions develop after the onset of bowel skin lesions develop after the onset of bowel symptomssymptoms ，， and patients frequently have and patients frequently have concomitant active peripheral arthritis. concomitant active peripheral arthritis.

The lesions of EN are hotThe lesions of EN are hot ，， redred ，， tender tender nodules measuring 1-5 cm in diameter and are nodules measuring 1-5 cm in diameter and are found on the anterior surface of the lower found on the anterior surface of the lower legslegs ，， anklesankles ，， calvescalves ，， thighsthighs ，， and arms. and arms.

Therapy is directed toward theunderlying Therapy is directed toward theunderlying bowel disease. bowel disease.

DermatologicDermatologic

Pyoderma gangrenosum (PG) Pyoderma gangrenosum (PG) is seen is seen in 1 - 12% of UC patients and less in 1 - 12% of UC patients and less ιommonly in Crohn's ιolitis. ιommonly in Crohn's ιolitis.

Although it usually presents after the Although it usually presents after the diagnosis of IBD.diagnosis of IBD.

PG may occur years before the onset of PG may occur years before the onset of bowel symptomsbowel symptoms

A course independent of the bowel A course independent of the bowel diseasedisease ，， respond poorly to colectomyrespond poorly to colectomy ，，and even develop years after and even develop years after proctocolectomy. proctocolectomy.


It is usually associated with severe disease. It is usually associated with severe disease. Lesions are commonly found on the dorsal Lesions are commonly found on the dorsal

surface of the feet and legs but may occur surface of the feet and legs but may occur on the armson the arms ，， chestchest ，， stomastoma ，， and even and even the face. PG usually begins as a pustule the face. PG usually begins as a pustule andthen spreads concentrically to rapidly andthen spreads concentrically to rapidly undermine healthy skin. Lesions then undermine healthy skin. Lesions then ulcerateulcerate ，， with violaceous edges with violaceous edges surrounded by a margin of erythema.surrounded by a margin of erythema.

CentrallyCentrally ，， they contain necrotic tissue they contain necrotic tissue with blood and exudates.with blood and exudates.


Lesions may be single or multiple Lesions may be single or multiple and grow as large as 30 cm. and grow as large as 30 cm.

They are sometimes very difficult to They are sometimes very difficult to treat and often require IV treat and often require IV antibiotics, IV glucocorticoidantibiotics, IV glucocorticoid ，， dapsonedapsone ，， azathioprineazathioprine ，，thalidomidethalidomide ，， IV cyclosporineIV cyclosporine ，， or or infliximabinfliximab


Other dermatologic manifestations Other dermatologic manifestations include include pyoderma vegetanspyoderma vegetans ，， which which occurs in intertriginous areas.occurs in intertriginous areas.

Pyostomatitis vegetansPyostomatitis vegetans ，， which which involves the mucous membranes.involves the mucous membranes.

Sweet syndromeSweet syndrome ，， a neutrophilic a neutrophilic dermatosis.dermatosis.

metastatic CDmetastatic CD ，， a rare disorder a rare disorder defined by cutaneous granuloma defined by cutaneous granuloma formation. formation.


PsoriasisPsoriasis affects 5 - 1 0% of patients with affects 5 - 1 0% of patients with IBD and is unrelated to bowel activity IBD and is unrelated to bowel activity consistent with the potential shared consistent with the potential shared immunogenetic basis of these diseases. immunogenetic basis of these diseases.

Perianal skin tags Perianal skin tags are found in 75-80% are found in 75-80% of patients with CDof patients with CD ，， especially those especially those with colon involvement. with colon involvement.

Oral mucosal lesionsOral mucosal lesions ，， seen often in seen often in CD and rarely in UCCD and rarely in UC ，， include aphthous include aphthous stomatitis and cobblestone" lesions of the stomatitis and cobblestone" lesions of the buccal mucosa.buccal mucosa.

RheumatologicRheumatologic

Peripheral arthritis develops in 1 5-20% Peripheral arthritis develops in 1 5-20% of IBD patientsof IBD patients ，， is more common in is more common in CDCD ，， and worsens with exacerbations of and worsens with exacerbations of bowel activity. bowel activity.

It is asymmetricIt is asymmetric ，， polyarticularpolyarticular ，， and and migratory and most often affects large migratory and most often affects large joints of the upper and lower extremities. joints of the upper and lower extremities.

Treatment is directed at reducing bowel Treatment is directed at reducing bowel inflammation. inflammation.

In severe UCIn severe UC ，， colectomy frequently colectomy frequently cures the arthritis.cures the arthritis.


Ankylosing spondylitis (AS) occurs in about Ankylosing spondylitis (AS) occurs in about 10% of IBD patients and is more common in 10% of IBD patients and is more common in CD than Uc. CD than Uc.

About two-thirds of IBD patients with AS About two-thirds of IBD patients with AS express the HLA-B27 antigen. The AS express the HLA-B27 antigen. The AS activity is not related to bowel activity and activity is not related to bowel activity and does not remit with glucocorticoids or does not remit with glucocorticoids or colectomy.colectomy.

It most often affects the spine and pelvisIt most often affects the spine and pelvis ，，producing symptoms of diffuse low-back producing symptoms of diffuse low-back painpain ，， buttock painbuttock pain ，， and morning and morning stiffness.stiffness.


The course is continuous and The course is continuous and progressiveprogressive ，， leading to permanent leading to permanent skeletal damage and deformity. skeletal damage and deformity.

Anti-TNF therapy reduces spinal Anti-TNF therapy reduces spinal inflammation and improves functional inflammation and improves functional status and quality of life. status and quality of life.

Sacroiliitis is symmetricSacroiliitis is symmetric ，， occurs occurs equally in UC and CDequally in UC and CD ，， is often is often asymptomaticasymptomatic ，， does not correlate with does not correlate with bowel activitybowel activity ，， and does not always and does not always progress to AS. progress to AS.


Other rheumatic manifestations Other rheumatic manifestations include hyper trophic include hyper trophic osteoarthropathyosteoarthropathy ，， pelvic!femoral pelvic!femoral osteomyelitisosteomyelitis ，， and relapsing and relapsing polychondritis.polychondritis.

OcularOcular The incidence of ocular complications in IBD The incidence of ocular complications in IBD

patients is 1 - 1 0%. patients is 1 - 1 0%. The most common are The most common are conjunctivitisconjunctivitis ，，

anterior uveitis/iritisanterior uveitis/iritis ，， and and episcleritis. episcleritis. Uveitis is associated with both UC and Crohn's Uveitis is associated with both UC and Crohn's

colitiscolitis may be found during periods of remissionmay be found during periods of remission may develop in patients following bowel may develop in patients following bowel

resection. resection. Symptoms include ocular painSymptoms include ocular pain ，，

photophobiaphotophobia ，， blurred visionblurred vision ，， and headache. and headache.

OcularOcular

Prompt interventionPrompt intervention ，， sometimes sometimes with systemic glucocorticoidswith systemic glucocorticoids ，， is is required to prevent scarring and required to prevent scarring and visual impairment.visual impairment.

OcularOcular

EpisderitisEpisderitis is a benign disorder that is a benign disorder that presents with synptoms of mild presents with synptoms of mild ocular burning. ocular burning.

It occurs in 3-4% of IBD patientsIt occurs in 3-4% of IBD patients more commonly in Crohn's colitismore commonly in Crohn's colitis is treated with topical is treated with topical

glucocorticoidsglucocorticoids

HepatobiliaryHepatobiliary

Hepatic steatosis Hepatic steatosis is detectable in is detectable in about one-half of the abnormal liver about one-half of the abnormal liver biopsies from patients with CD and UC; biopsies from patients with CD and UC; patients usually present with patients usually present with hepatomegaly. hepatomegaly.

Fatty liver Fatty liver usually results from a usually results from a combination of chronic debilitating combination of chronic debilitating illness, malnutrition, and glucocorticoid illness, malnutrition, and glucocorticoid therapy. therapy.

CholelithiasisCholelithiasis occurs in 10-35% of CD occurs in 10-35% of CD patients with ileitis or ileal resection. patients with ileitis or ileal resection.


Gallstone formation is caused by Gallstone formation is caused by malabsorption of bile acids, resulting in malabsorption of bile acids, resulting in depletion of the bile salt pool and the depletion of the bile salt pool and the secretion of lithogenic bile. secretion of lithogenic bile.

Primary sclerosing cholangitis (PSC) Primary sclerosing cholangitis (PSC) is a is a disorder characterized by both intrahepatic disorder characterized by both intrahepatic and extrahepatic bile duct inflammation and and extrahepatic bile duct inflammation and fibrosis.fibrosis.

Frequently leading to biliary cirrhosis and Frequently leading to biliary cirrhosis and hepatic failure.hepatic failure.

5% of patients with UC have PSC, but 50-5% of patients with UC have PSC, but 50-75% of patients with PSC have IBD. 75% of patients with PSC have IBD.


PSC occurs less often in patients with PSC occurs less often in patients with CD. CD.

Although it can be recognized after the Although it can be recognized after the diagnosis of IBDdiagnosis of IBD

PSC can be detected earlier or even PSC can be detected earlier or even years after proctocolectomy. years after proctocolectomy.

Consistent with this, the immunogenetic Consistent with this, the immunogenetic basis for PSC appears to be overlappingbasis for PSC appears to be overlapping

IBD and PSC are commonly IBD and PSC are commonly pANCApANCA positive. positive.


Most patients have no symptoms at the time Most patients have no symptoms at the time of diagnosis; when symptoms are presentof diagnosis; when symptoms are present ，，they consist of fatigue, jaundice, abdominal they consist of fatigue, jaundice, abdominal painpain ，， fever, anorexia, and malaise. fever, anorexia, and malaise.

The traditional gold standard diagnostic test is The traditional gold standard diagnostic test is endoscopic retrograde cholangiopancrea endoscopic retrograde cholangiopancrea tography tography (ERCP)(ERCP)

magnetic resonance magnetic resonance cholangiopancreatography cholangiopancreatography (MRCP) (MRCP) is also is also sensitive and specific. sensitive and specific.

MRCP is reasonable as an initial diagnostic MRCP is reasonable as an initial diagnostic test in children and.test in children and.


In patients with PSC. both ERCP and In patients with PSC. both ERCP and MRCP demonstrate multiple bile duct MRCP demonstrate multiple bile duct strictures alternating with relatively strictures alternating with relatively normal segments. normal segments.

The bile acid ursodeoxycholic acid The bile acid ursodeoxycholic acid (ursodiol) may reduce alkaline phosphatase (ursodiol) may reduce alkaline phosphatase and serum aminotransferase levelsand serum aminotransferase levels ，， but but histologic improvement has been marginal. histologic improvement has been marginal.

High doses (25-30 mg/kg per day) may High doses (25-30 mg/kg per day) may decrease the risk of colorectal dysplasia decrease the risk of colorectal dysplasia and cancer in patientswith UC and PSc. and cancer in patientswith UC and PSc.


Endoscopic stenting may be palliative for Endoscopic stenting may be palliative for cholestasis secondary to bile duct cholestasis secondary to bile duct obstruction. obstruction.

Patients with symptomatic disease develop Patients with symptomatic disease develop cirrhosis and liver failure over 5 - 1 0 years cirrhosis and liver failure over 5 - 1 0 years and eventually require liver transplantation.and eventually require liver transplantation.

PSC patients have a 10- 1 5% lifetime risk of PSC patients have a 10- 1 5% lifetime risk of developing cholangiocarcinoma and then developing cholangiocarcinoma and then cannot be transplanted Patients with IBD cannot be transplanted Patients with IBD and PSC are at increased risk of colon and PSC are at increased risk of colon cancer and should be surveyed yearly by cancer and should be surveyed yearly by colonoscopy and biopsy.colonoscopy and biopsy.


Cholangiography is normal in a small Cholangiography is normal in a small percentage of patients who have a variant of percentage of patients who have a variant of PSC known as small duct primary sclerosing PSC known as small duct primary sclerosing cholangitis. cholangitis.

This variant (sometimes referred to as This variant (sometimes referred to as "pericholangitis") is probably a form of PSC "pericholangitis") is probably a form of PSC involving small-caliber bile ducts. involving small-caliber bile ducts.

It has similar biochemical and histologic It has similar biochemical and histologic features to classic PSc. features to classic PSc.

It appears to have a significantly better It appears to have a significantly better prognosis than classic PSCprognosis than classic PSC ，， although it may although it may evolve into classic PSc. evolve into classic PSc.


Granulomatous hepatitis and hepatic Granulomatous hepatitis and hepatic amyloidosis are much rarer amyloidosis are much rarer extraintestinal manifestations of extraintestinal manifestations of IBD.IBD.

UrologicUrologic

The most frequent genitourinary The most frequent genitourinary complications are calculicomplications are calculi ，， ureteral ureteral obstructionobstruction ，， and ileal bladder fistulas. and ileal bladder fistulas.

The highest frequency of nephrolithiasis The highest frequency of nephrolithiasis ( 1 0-20%) occurs in patients with CD ( 1 0-20%) occurs in patients with CD following small bowelresection. following small bowelresection.

Calcium oxalate stones develop Calcium oxalate stones develop secondary to hyperoxaluriasecondary to hyperoxaluria ，， which which results from increased absorption of results from increased absorption of dietary oxalate. dietary oxalate.

UrologicUrologic

NormallyNormally ，， dietary calcium combines with dietary calcium combines with luminal oxalate to form insoluble calcium luminal oxalate to form insoluble calcium oxalateoxalate ，， which is eliminated in the stool. which is eliminated in the stool.

In patients with ileal dysfunctionIn patients with ileal dysfunction ，，howeverhowever ，， nonabsorbed fatty acids bind nonabsorbed fatty acids bind calcium and leaveoxalate unbound. calcium and leaveoxalate unbound.

The unbound oxalate is then delivered to The unbound oxalate is then delivered to the colon, where it is readily absorbedthe colon, where it is readily absorbed ，，especially in the presence of inflammation especially in the presence of inflammation hepatitis and hepatic amyloidosis are much hepatitis and hepatic amyloidosis are much rarer extraintestinal manifestations of IBD.rarer extraintestinal manifestations of IBD.

Metabolic Bone DiseaseMetabolic Bone Disease

Low bone mass occurs in 3-30% of IBD Low bone mass occurs in 3-30% of IBD patients. patients.

The risk is increased by glucocorticoidsThe risk is increased by glucocorticoids ，，cyclosporinecyclosporine ，， methotrexatemethotrexate ，， and total and total parenteral nutrition (TPN) . parenteral nutrition (TPN) .

Malabsorption and inflammation mediated by Malabsorption and inflammation mediated by IL- 1 IL- 1 ，， ILIL 66 ，， TNFTNF ，， and other and other inflammatory mediators also contribute t o inflammatory mediators also contribute t o low bone density. low bone density.

An increased incidence of hipAn increased incidence of hip ，， spinespine ，，wristwrist ，， and rib fractures has been noted: and rib fractures has been noted: 36% in CD and 45% in Uc. 36% in CD and 45% in Uc.


The absolute risk of an osteoporotic fracture The absolute risk of an osteoporotic fracture is about 1 % per person per year. is about 1 % per person per year.

Fracture ratesFracture rates ，， particularly in the spine and particularly in the spine and hiphip ，， are highest among the elderly (age are highest among the elderly (age >60). >60).

One study noted an OR of 1 .72 for vertebral One study noted an OR of 1 .72 for vertebral fracture and an OR of 1 .59 for hip fracture. fracture and an OR of 1 .59 for hip fracture.

The disease severity predicted the risk of a The disease severity predicted the risk of a fracture. fracture.

Only 1 3 % of IBD patients who had a fracture Only 1 3 % of IBD patients who had a fracture were on any kind of antifracture treatment. were on any kind of antifracture treatment.


Up to 20% of bone mass can be lost Up to 20% of bone mass can be lost per year with chronic glucocorticoid per year with chronic glucocorticoid use. use.

The effect is dosage-dependent. The effect is dosage-dependent. Budesonide may also suppress the Budesonide may also suppress the

pituitary-adrenal axis and thus carries pituitary-adrenal axis and thus carries a risk of causing osteoporosis. a risk of causing osteoporosis.

Osteonecrosis is characterized by Osteonecrosis is characterized by death of osteocytes and adipocytes death of osteocytes and adipocytes and eventual bone collapse. and eventual bone collapse.


The pain is aggravated by motion and The pain is aggravated by motion and swelling of the joints. swelling of the joints.

It affects the hips more often than knees It affects the hips more often than knees and shouldersand shoulders ，， and in one seriesand in one series ，， 4.3% 4.3% of patients developed osteonecrosis within of patients developed osteonecrosis within 6 months of starting glucocorticoids. 6 months of starting glucocorticoids.

Diagnosis is made by bone scan or MRIDiagnosis is made by bone scan or MRI ，，and treatment consists of pain controland treatment consists of pain control ，，cord decompressioncord decompression ，， osteotomyosteotomy ，， and and joint replacement.joint replacement.

Thromboembolic DisorderThromboembolic Disorder Patients with IBD risk of both venous and arterial Patients with IBD risk of both venous and arterial

thrombosis even if the disease is not active. thrombosis even if the disease is not active. Factors responsible for the hypercoagulable state: d: Factors responsible for the hypercoagulable state: d:

abnormalities of the plateletendothelial interactionabnormalities of the plateletendothelial interaction HyperhomocysteinemiaHyperhomocysteinemia alterations in the coagulation cascadealterations in the coagulation cascade impaired fibrinolysisimpaired fibrinolysis involvement of tissue factor-bearing microvesiclesinvolvement of tissue factor-bearing microvesicles disruption of coagulation system by autoantibodiesdisruption of coagulation system by autoantibodies genetic predisposition. genetic predisposition.

A spectrum of vasculitides involving smallA spectrum of vasculitides involving small ，，mediummedium ，， and large vessels has also been observed.and large vessels has also been observed.

Extra-intestinal manifestations Extra-intestinal manifestations of IBDof IBD

Liver and Biliary tract disease:Liver and Biliary tract disease: Pericholangitis, fatty infiltration, PSC Pericholangitis, fatty infiltration, PSC

(1-4%, more with UC), (1-4%, more with UC), cholangiocarcinoma, gallstonescholangiocarcinoma, gallstones

Thromboembolic disease, vasculitis, Thromboembolic disease, vasculitis, Renal disease (urolithiasis, GN), Renal disease (urolithiasis, GN), clubbing, amyloidosis.clubbing, amyloidosis.

EyeEyeinflammationinflammation**

Liver andLiver andbile ductbile duct

inflammationinflammation

Skin lesionsSkin lesions

Arthritis and Arthritis and joint painsjoint pains

KidneyKidneystonesstones

Growth failureGrowth failurein childrenin children

LowerLowerbone densitybone density**

SubfertilitySubfertility**

IBD: Systemic IBD: Systemic ComplicationsComplications

**Higher incidence in womenHigher incidence in women..

GallstonesGallstones

OvariesOvaries

UterusUterus

Complications of IBDComplications of IBD

BleedingBleeding StrictureStricture FistulaFistula Toxic megacolonToxic megacolon CancerCancer

Complications of Complications of IBDIBD

Treatment Treatment

Goals of therapyGoals of therapy Induce and maintain remission.Induce and maintain remission. Ameliorate symptomsAmeliorate symptoms Improve pts quality of lifeImprove pts quality of life Adequate nutritionAdequate nutrition Prevent complication of both the Prevent complication of both the

disease and medicationsdisease and medications

5-Aminosalicylic Acids5-Aminosalicylic Acids

The mainstay treatment of mild to moderately active UC and CD (induction).

5-ASA may act by blocking the production of prostaglandins

and leukotrienes, inhibiting bacterial peptide–induced

neutrophil chemotaxis and adenosine-induced secretion,

scavenging reactive oxygen metabolites

5-Aminosalicylic Acids5-Aminosalicylic Acids

For patients with distal colonic disease, a suppository or enema form will be most appropriate.

Maintenance treatment with a 5-aminosalicylic acid can be effective for sustaining remission in ulcerative colitis but is of questionable value in Crohn's disease.

Corticosteroids

Topical corticosteroids can be used as an alternative to 5-ASA in ulcerative proctitis or distal UC.

Oral prednisone or prednisolone is used for moderately severe UC or CD, in doses ranging up to 60 mg per day.

IV is warranted for patients who are sufficiently ill to require hospitalization; the majority will have a response within 7 to 10 days.

CorticosteroidsCorticosteroids No proven maintenance benefit in No proven maintenance benefit in

the treatment of either UC or CD. the treatment of either UC or CD. Many and serious side effects. Many and serious side effects. Budesonide: Budesonide:

less side effects, less side effects, its use is limited to patients with distal its use is limited to patients with distal

ileal and right-sided colonic diseaseileal and right-sided colonic disease

Immunosuppressive Agents

These agents are generally appropriate for patients in whom the dose of corticosteroids cannot be tapered or discontinued.

Azathioprine & 6-MP The most extensively used immunosuppressive agents. The mechanisms of action unknown but may include

suppressing the generation of a specific subgroup of T cells. The onset of benefit takes several weeks up to six The onset of benefit takes several weeks up to six

months.months. Dose-related BM suppression is uniformly observedDose-related BM suppression is uniformly observed

Immunosuppressive Agents MethotrexateMethotrexate

Effective in steroid-dependent active Effective in steroid-dependent active CD and in maintaining remission.CD and in maintaining remission.

CyclosporineCyclosporine Severe UC not responding to IV steroid Severe UC not responding to IV steroid

&need urgent proctocolectomy.&need urgent proctocolectomy. 50% of the responders will need 50% of the responders will need

surgery within a year.surgery within a year.

Anti-TNF Therapy: Anti-TNF Therapy: Infliximab Infliximab

It is a chimeric monoclonal antibody, binds soluble TNF.

Prompt onset, effects takes 6weeks to max of 6m.

Indicated in fisulizing crohns, refractory CD and refractory UC

Complications (it is safe and usu tolerable) Acute infusion reactions, which may include

chest tightness, dyspnea, rash, and hypotension. Delayed hypersensitivity reactions, consisting of

severe polyarthralgia, myalgia, facial edema, urticaria, or rash, are an unusual complication occurring from 3 to 12 days after an infusion.

Infliximab: side effectsInfliximab: side effects

Increase risk of upper respiratory infections.

Any patient suspected of having a pyogenic complication of CD or any serious infection should undergo adequate drainage and treatment with antibiotics before starting infliximab.

Reactivation of tuberculosis has been observed and has resulted in disseminated disease and death.

INDICATIONS FOR SURGERYINDICATIONS FOR SURGERY

In patients with UC:In patients with UC: Severe attacks that fail to respond to medical therapy. Severe attacks that fail to respond to medical therapy. Complications of a severe attack (e.g., perforation, Complications of a severe attack (e.g., perforation,

acute dilatation). acute dilatation). Chronic continuous disease with an impaired quality Chronic continuous disease with an impaired quality

of life. of life. Dysplasia or carcinoma.Dysplasia or carcinoma.

In patients with CDIn patients with CD Obstruction, severe perianal disease unresponsive to Obstruction, severe perianal disease unresponsive to

medical therapy, difficult fistulas, major bleeding, medical therapy, difficult fistulas, major bleeding, severe disabilitysevere disability

30 % relapse rate30 % relapse rate

IBD Sequelae IBD Sequelae UC:UC:

Risk of cancer begins after 8 years, risk of Risk of cancer begins after 8 years, risk of pancolitis 7% at 20 years and 17% at 30 pancolitis 7% at 20 years and 17% at 30 years.years.

Increased risk: early age of onset, pancolitis.Increased risk: early age of onset, pancolitis. Need for colonoscopic screening after 8 yearsNeed for colonoscopic screening after 8 years

CD:CD: True incidence of cancer is uncertain, but True incidence of cancer is uncertain, but

could be as high as UCcould be as high as UC Need the same screening policy.Need the same screening policy.

IBD conclusionIBD conclusion

It is a chronic disordersIt is a chronic disorders Need to exclude other possibilitiesNeed to exclude other possibilities Need to differentiate between the Need to differentiate between the

twotwo Need long term management with Need long term management with

primary goal to induce then maintain primary goal to induce then maintain remission and prevent complications remission and prevent complications of both the disease and drugs.of both the disease and drugs.

Documents

Inflammatory Bowel Disease E Rahimi, MD Assiatant Professor Department Of Internal Medicine MUK